ENAapplication/xmlftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/073/SRR24065973/SRR24065973_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/071/SRR24065971/SRR24065971_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/075/SRR24065975/SRR24065975_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/079/SRR24065979/SRR24065979_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/078/SRR24065978/SRR24065978_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/071/SRR24065971/SRR24065971_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/072/SRR24065972/SRR24065972_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/074/SRR24065974/SRR24065974_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/077/SRR24065977/SRR24065977_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/072/SRR24065972/SRR24065972_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/074/SRR24065974/SRR24065974_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/078/SRR24065978/SRR24065978_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/076/SRR24065976/SRR24065976_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/075/SRR24065975/SRR24065975_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/070/SRR24065970/SRR24065970_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/070/SRR24065970/SRR24065970_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/073/SRR24065973/SRR24065973_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/079/SRR24065979/SRR24065979_1.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/077/SRR24065977/SRR24065977_2.fastq.gzftp://ftp.sra.ebi.ac.uk/vol1/fastq/SRR240/076/SRR24065976/SRR24065976_1.fastq.gzprimaryOK200GenomicsUniversity of Regensburghttps://www.ebi.ac.uk/ena/browser/view/PRJNA952234Plasmodium falciparumThe complex life cycle of the malaria parasite Plasmodium falciparum (Pf) and the accompanying transcriptional variation is only explained in part by stage-specific transcription factors like the ApiAP2 family, as these factors are strongly under-represented in Pf. Global and local changes in chromatin structure during life cycle progression suggest the contribution of epigenetic mechanisms as a critical mechanism for fine-tuning gene regulation during malaria parasite development. Pf chromatin is largely unexplored and is distinct from other eukaryotes in many respects. This is likely to accommodate the highly A/T-rich genome which averages over 90% in non-coding regions, the highest of any known eukaryote. We characterized PF3D7_1104200 (PfSnf2L), an ATPase-containing protein that is related to ISWI-type chromatin remodeling enzymes (CREs). Using a conditional knockout (KO) system, we demonstrate that PfSnf2L is essential for parasite development, globally controls just-in-time transcription regulation, and specifically represses gametocyte-specific gene expression. Characterization of the enzymatic activity in vitro, combined with mapping chromatin organization in vivo revealed that PfSnf2L shapes the promotor architecture of stage-specific genes through its nucleosome remodeling activity, thereby influencing gene activation and repression. The unique properties of the Plasmodium Snf2L allowed screening and identification of a specific inhibitor that specifically kills the parasite, phenocopies the loss of correct gene expression timing, and inhibits the formation of gametocytes. Overall design: Comparative nucleosome profiling analysis of MNase-seq data of 3D7 parasites with PfSnf2L-KO induced vs. non induced, for two different induction timepoints.pathogen:protozoanpathogenprotozoaENAsingle-organism biosynthetic process, Epigenetic, Effects, Longterm, Long Term Effects, Longterm Effect, MNase-seq assay., Long-Term Effect, MNase-seq, Epigenetics, Long-Term, regulator, Effect, Long-Term Effects, Epigenomic, Long Term, Longterm Effects, multicellular organismal biosynthetic processsingle-organism biosynthetic process, Epigenetic, Effects, Longterm, Long Term Effects, Longterm Effect, MNase-seq assay., Long-Term Effect, MNase-seq, Epigenetics, Long-Term, regulator, Effect, Long-Term Effects, Epigenomic, Long Term, Longterm Effects, multicellular organismal biosynthetic processfalsePfSnf2L - an epigenetic regulator of just-in-time expression and gametocyte formation [MNase-Seq]PfSnf2L - an epigenetic regulator of just-in-time expression and gametocyte formation [MNase-Seq]2025-09-242024-10-19PRJNA952234GSE2289475833